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Biomedical subjects

K Sawada

Publications and source records attributed to K Sawada.

At least 109 records · Page 6Linked to original sources

[The role of a university hospital in home medical care--analysis of nurses' activities].

The purpose of this study was to clarify the role of nurses in the Department of In-Home Medical Care, a university hospital cooperating with primary care physicians, visiting nurse stations, and health stations in the community. Nurses coordinated between departments in the University Hospital and between the community for patients who were in the terminal stage and/or were provided complex home medical treatments. Nurses' activities in coordination were longer and more frequent than patient education for discharge.

Community Health Nursing↗

Hepatic grooves and portal segmentation.

The aim of the present study was to examine the topographical relationship between the locations of the grooves and the borders of Couinaud's portal segments. We found 79 grooves on the diaphragmatic surfaces of 50 livers from 420 cadavers. Most grooves were located within segment VIII wholly (31/79) or partially (39/79). By contrast, only 11 grooves corresponded to the border between two segments (segments VIII/IV in 6 cases and segments VIII/VII in 5 cases). Diaphragmatic indentations (fold-like protrusions) into the groove were observed in 1 case. Our results suggest that the grooves did not form during the early embryonic period when intrahepatic vessels and ducts ramify, but that they formed during a later stage of diaphragmatic growth after establishment of the basic segmental configuration of the liver. The grooves do not seem to be critical landmarks for segmental borders of the liver.

Aged↗

Abnormal expression of tyrosine hydroxylase immunoreactivity in Purkinje cells precedes the onset of ataxia in dilute-lethal mice.

Expression of tyrosine hydroxylase (TH) immunostaining in the cerebellum was examined in dilute-lethal mice (DL) prior to and following the onset of ataxia. DL walked normally on postnatal days 7 and 8. Falling over when walking was exhibited by about 20% of DL on day 9 and by all DL by day 10. TH-positive Purkinje cells in lobules IX and X of the vermis of either ataxic or non-ataxic DL were clearly observed on day 9 when compared to control mice, and had drastically increased by day 10. These results revealed that abnormal TH expression occurred in some Purkinje cells of DL cerebella, preceding the onset of ataxia.

Animals↗

Histiocyte reaction in rabbit femurs to UHMWPE, metal, and ceramic particles in different sizes.

To assess the histologic reaction caused by biomaterial particles in different sizes around the bone-implant interface, we examined ultra-high molecular weight polyethylene (UHMWPE, average diameter of 11 microm), UHMWPE (99 microm), cobalt-chromium alloy (Co-Cr, 3.9 microm), stainless steel (SUS316L, 3.9 microm), alumina ceramics (3.9 microm), titanium alloy (Ti, 3.5 microm), Co-Cr (0.03 microm), and Ti (0.03 microm). After the longitudinal groove on a polymethylmethacrylate plug was filled with one type of the particles, the plug was inserted into the medullar canal of the distal end of rabbit femurs, and tissue block was resected 4 and 12 weeks after the insertion. Histiocytes were markedly accumulated around the particles of UHMWPE (11 microm), Co-Cr (3.9 microm), SUS316L (3.9 microm), Co-Cr (0.03 microm), and titanium alloy (0.03 microm). Around the UHMWPE particles (99 microm), a slight histiocytic reaction and bone formation were observed. Particles of alumina ceramics (3.9 microm) and titanium alloy (3.5 microm) which were in phagocytosable sizes also had few histiocytic reactions. Statistically, the material difference was more strongly related to the histiocyte reaction than to the particle size and calculated total surface area of particles. Our findings demonstrate that particles of different biomaterials and in different sizes induce different foreign-body histological reactions.

Aluminum Oxide↗

Abnormal expression of tyrosine hydroxylase immunoreactivity in cerebellar cortex of ataxic mutant mice.

Expression of tyrosine hydroxylase (TH) was examined immunohistochemically in the cerebellum of two ataxic mutants, Rolling mouse Nagoya (RMN) and dilute-lethal mice (DL). In littermate controls of both mutants, a few TH-positive Purkinje cells were distributed sparsely and their number was smaller than in the mutants at any ages examined. In RMN, TH-positive Purkinje cells were distributed in lobule IX and X, and were arranged into parasagittal bands at 2 weeks of age. TH-positive Purkinje cells increased in number and were widely distributed throughout the vermis at 3 weeks of age. In adult RMN, TH-positive Purkinje cells were found in all lobules of the cerebellum. Their parasagittal bands also became evident in the hemisphere. In DL, TH-positive Purkinje cells were mainly distributed in vermal lobules IX and X, and the flocculus at 3 weeks of age. They were also found as bands in lobules IX and X. The results suggest that abnormal expression of TH in Purkinje cells may not be specific to the allelic group. Since TH promoter is activated by Ca2+, TH expression in the mutant Purkinje cells may predict neuronal dysfunction caused by alterations in cellular Ca2+ currents.

Animals↗

Molecular cloning of cDNA encoding human Rab3D whose expression is upregulated with myeloid differentiation.

To identify genes expressed in myeloid differentiation, we isolated a cDNA fragment by differential display using RNA prepared from HT93A cells, a human cell line capable of differentiating into neutrophil and eosinophil lineages in response to retinoic acid (RA). Evaluation of the full-length clone isolated from an HT93A cDNA library showed that it encoded a 24 kDa protein comprised of several domains conserved in the Ras superfamily. Comparison of the deduced amino acid sequence of this clone with Rab proteins revealed that it had highest homology to a small GTP-binding protein, murine Rab3D. The mRNA expression of human Rab3D was upregulated in the course of myeloid differentiation, and it was preferentially expressed in granulocytes. These results suggest that human Rab3D may play a specific role in granulocytes, for example in exocytosis of neutrophil-specific granules or in degranulation of both eosinophils and basophils.

Amino Acid Sequence↗

Abnormal distribution of hippocampal mossy fibers in rats exposed to X-irradiation in utero.

The effects of prenatal X-irradiation (0.3, 0.6, 1.2 or 1.8 Gy) on the hippocampal development were examined at six weeks of age in rats. The laminar structure of the hippocampus was deranged in the rats exposed to 0.6 Gy or more. Pyramidal cells in the CA-3 region were more susceptible than those in the CA-1 region. Aberrant mossy fiber terminals were observed in the stratum oriens of the CA-3 region (infrapyramidal mossy fibers) in rats exposed to 0.3 Gy or more.

Animals↗

Beta2-glycoprotein I is necessary to inhibit protein C activity by monoclonal anticardiolipin antibodies.

OBJECTIVE: To clarify mechanisms of the thrombosis associated with anticardiolipin antibodies (aCL), we examined the effects on activated protein C (APC) of monoclonal aCL and beta2-glycoprotein I (beta2GPI), which is required for formation of the epitopes of aCL. METHODS: We developed the chromogenic assay, in which the degradation of coagulation factor Va by APC is reflected in the reduced generation of thrombin from prothrombin, using soybean trypsin inhibitor to inhibit APC. APC activities were measured in the presence and absence of 3.4 microM beta2GPI and/or 2.5 microg/ml of IgM monoclonal aCL (EY2C9 and EY1C8) established from peripheral blood lymphocytes obtained from a patient with aCL. RESULTS: Without APC, the formed thrombin activity decreased by the addition of 3.4 microM beta2GPI. When 12.8 nM APC was added, beta2GPI partially reversed the APC-induced inhibition of thrombin generation in a concentration-dependent manner. With 3.4 microM beta2GPI, the thrombin generation in monoclonal aCL (2.5 microg/ml) decreased to 77.1-80.2% by the addition of 12.8 nM APC, but the values were above that in the control IgM (72.7%). Without beta2GPI, the APC activity was unaffected by the addition of monoclonal aCL. CONCLUSION: Beta2-glycoprotein I exhibits procoagulant activity by inhibiting APC activity and anticoagulant activity by inhibiting thrombin generation. Any further inhibition of APC activity was caused by monoclonal aCL and only in the presence of beta2GPI.

Adenomatous Polyposis Coli Protein↗

Role of physiologic concentrations of stem cell factor in leukemic type growth of myelodysplastic CD34+ cells.

The stem cell factor (SCF: a ligand for c-kit) plays a central role in the growth of myelodysplastic (MDS) progenitor cells with leukemic type growth. In this study, the role of physiologic concentrations of SCF on the proliferation and differentiation on MDS progenitor cells was further analyzed in the presence of combined cytokines. For this purpose, marrow CD34+ cells were purified up to 94% for 12 normal individuals and 90% for 18 MDS patients, using monoclonal antibodies and immunomagnetic microspheres. The purified CD34+ cells were cultured for 14 days with saturating doses of cytokines, including recombinant human macrophage colony stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte/macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3) and rSCF. The clonal growth of MDS CD34+ cells supported by a combination of all the above cytokines was then subdivided into the two patterns of leukemic or non-leukemic. The role of various concentrations of rSCF (0, 0.5, 5, 50 and 500 ng ml(-1)), with or without the above cytokines, in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. The physiologic concentration of SCF at 5 ng ml(-1) significantly increased undifferentiated 'blast cell' colonies or clusters in leukemic type growth of MDS CD34+ cells over that seen in normal CD34+ cells. SCF is present in plasma at a level of ng ml(-1). This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blasts.

Antigens, CD34↗

Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2.

1 Glibenclamide is a widely used sulphonylurea for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). This agent has been reported to inhibit the activities of various ion channels and transporters. In the present study, we examined the effects of glibenclamide on the function of the H+/peptide cotransporters PEPT1 and PEPT2 by using stable transfectants. 2 Uptake of [14C]-glycylsarcosine, a typical substrate for peptide transporters, by PEPT1- or PEPT2-expressing transfectant was inhibited by glibenclamide as well as other sulphonylureas including tolbutamide. 3 Kinetic analysis revealed that the inhibition by glibenclamide was noncompetitive. Dixon plot analyses showed that the Ki values of this agent were 25 and 7.8 microM for PEPT1 and PEPT2, respectively. 4 Glibenclamide did not inhibit Na+-coupled alanine and alpha-methyl-D-glucoside transport, suggesting that the inhibitory effects of glibenclamide on peptide transporters were not due to nonspecific interactions. 5 There was little uptake of [3H]-glibenclamide by PEPT-expressing transfectants as compared to mock-transfected cells, suggesting that glibenclamide was not a substrate for these peptide transporters. 6 In summary, glibenclamide inhibited the [14C]-glycylsarcosine transport by PEPT1 and PEPT2 in a noncompetitive fashion, although glibenclamide per se was not transported through these transporters. These findings would provide important information for clinical, physiological and biochemical aspects of peptide transporters.

Alanine↗

Serum levels of thyroid-stimulating hormone receptor antibodies during IFN-alpha2a treatment of chronic hepatitis C.

Twenty chronic hepatitis C patients with baseline levels of thyroid hormones, antithyroglobulin, and antimicrosomal antibodies within the normal range were monitored by thyroid testing during a 26-week treatment with interferon-alpha2a (IFN-alpha2a). The present study was aimed at retrospectively analyzing thyroid-stimulating hormone (TSH) receptor antibodies, employing stored serum samples obtained from these patients at baseline, at 12 weeks, and at the end of IFN-alpha2a treatment. Ten patients (group A) received IFN-alpha2a at a total dose of 474 million units (MU), and 10 patients (group B) at a total dose of 774 MU. None of the patients produced antithyroglobulin and antimicrosomal antibodies. Two patients in group A exhibited elevated TSH levels without free thyroid hormone alterations while on the treatment. At baseline, 1 patient in group A had a positive TSH binding inhibitory immunoglobulin, and 1 patient in group B was positive for thyroid-stimulating antibody at the end of treatment. Both patients remained euthyroid throughout the treatment. Treatment with IFN-alpha2a may infrequently induce the production of TSH receptor antibodies in chronic hepatitis C patients provided preexisting autoimmune thyroid disease is precluded.

Adult↗

Specific cutaneous lesions of the scalp in myelodysplastic syndrome with deletion of 20q.

We reported a specific skin lesion on the scalp in a patient with myelodysplastic syndrome (MDS), treated as refractory anemia with excess of blasts (RAEB). Histologically, a specimen from a nodule of the scalp consisted of a diffuse infiltration of atypical cells in the dermis and subcutaneous tissue. The patient died of acute leukemia 3 months later. Chromosomal examination of bone marrow cells revealed deletion of 20q and 21 trisomy. The specific cutaneous lesions in this patient were associated with acute transformation. The deletion of 20q and specific cutaneous lesions are regarded as signs of poor prognosis.

Biopsy, Needle↗

Identification by subtractive hybridization of a novel insertion sequence specific for virulent strains of Porphyromonas gingivalis.

Subtractive hybridization was employed to isolate specific genes from virulent Porphyromonas gingivalis strains that are possibly related to abscess formation. The genomic DNA from the virulent strain P. gingivalis W83 was subtracted with DNA from the avirulent strain ATCC 33277. Three clones unique to strain W83 were isolated and sequenced. The cloned DNA fragments were 885, 369, and 132 bp and had slight homology with only Bacillus stearothermophilus IS5377, which is a putative transposase. The regions flanking the cloned DNA fragments were isolated and sequenced, and the gene structure around the clones was revealed. These three clones were located side-by-side in a gene reported as an outer membrane protein. The three clones interrupt the open reading frame of the outer membrane protein gene. This inserted DNA, consisting of three isolated clones, was designated IS1598, which was 1,396 bp (i.e., a 1,158-bp open reading frame) in length and was flanked by 16-bp terminal inverted repeats and a 9-bp duplicated target sequence. IS1598 was detected in P. gingivalis W83, W50, and FDC 381 by Southern hybridization. All three P. gingivalis strains have been shown to possess abscess-forming ability in animal models. However, IS1598 was not detected in avirulent strains of P. gingivalis, including ATCC 33277. The IS1598 may interrupt the synthesis of the outer membrane protein, resulting in changes in the structure of the bacterial outer membrane. The IS1598 isolated in this study is a novel insertion element which might be a specific marker for virulent P. gingivalis strains.

Amino Acid Sequence↗

Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata.

1,4,5,6-Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid (ectoine) is an excellent osmoprotectant. The biosynthetic pathway of ectoine from aspartic beta-semialdehyde (ASA), in Halomonas elongata, was elucidated by purification and characterization of each enzyme involved. 2,4-Diaminobutyrate (DABA) aminotransferase catalyzed reversively the first step of the pathway, conversion of ASA to DABA by transamination with L-glutamate. This enzyme required pyridoxal 5'-phosphate and potassium ions for its activity and stability. The gel filtration estimated an apparent molecular mass of 260 kDa, whereas molecular mass measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was 44 kDa. This enzyme exhibited an optimum pH of 8.6 and an optimum temperature of 25 degreesC and had Kms of 9.1 mM for L-glutamate and 4.5 mM for DL-ASA. DABA acetyltransferase catalyzed acetylation of DABA to gamma-N-acetyl-alpha,gamma-diaminobutyric acid (ADABA) with acetyl coenzyme A and exhibited an optimum pH of 8.2 and an optimum temperature of 20 degreesC in the presence of 0.4 M NaCl. The molecular mass was 45 kDa by gel filtration. Ectoine synthase catalyzed circularization of ADABA to ectoine and exhibited an optimum pH of 8.5 to 9.0 and an optimum temperature of 15 degreesC in the presence of 0.5 M NaCl. This enzyme had an apparent molecular mass of 19 kDa by SDS-PAGE and a Km of 8.4 mM in the presence of 0. 77 M NaCl. DABA acetyltransferase and ectoine synthase were stabilized in the presence of NaCl (>2 M) and DABA (100 mM) at temperatures below 30 degreesC.

Acetyltransferases↗

Functional characteristics of basolateral peptide transporter in the human intestinal cell line Caco-2.

The apical H+-coupled peptide transporter (PEPT1) and basolateral peptide transporter in human intestinal Caco-2 cells were functionally compared by the characterization of [14C]glycylsarcosine transport. The glycylsarcosine uptake via the basolateral peptide transporter was less sensitive to medium pH than uptake via PEPT1 and was not transported against the concentration gradient. Kinetic analysis indicated that glycylsarcosine uptake across the basolateral membranes was apparently mediated by a single peptide transporter. Small peptides and beta-lactam antibiotics inhibited glycylsarcosine uptake by the basolateral peptide transporter, and these inhibitions were revealed to be competitive. Comparison of the inhibition constant values of various beta-lactam antibiotics between PEPT1 and the basolateral peptide transporter suggested that the former had a higher affinity than the latter. A histidine residue modifier, diethyl pyrocarbonate, inhibited glycylsarcosine uptake by both transporters, although the inhibitory effect was greater on PEPT1. These findings suggest that a single facilitative peptide transporter is expressed at the basolateral membranes of Caco-2 cells and that PEPT1 and the basolateral peptide transporter cooperate in the efficient transepithelial transport of small peptides and peptidelike drugs.

Caco-2 Cells↗

Anti-obesity and anti-diabetic activities of a new beta3 adrenergic receptor agonist, (S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-propenyl] phenoxy] acetic acid ethanedioic acid (SWR-0342SA), in KK-Ay mice.

We investigated the beta-adrenergic receptor (AR) agonistic activities in rats and humans, and the anti-obesity and anti-diabetic activities in KK-Ay mice, of a new beta3-AR agonist, SWR-0342SA ((S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-pro penyl]phenoxy] acetic acid ethanedioic acid). With regards to its beta-AR agonistic activity in rats, SWR-0342SA stimulated the atrial beating rate (beta1-AR activity) and white adipocyte lipolysis (beta3-AR activity), but did not induce uterine muscle relaxation (beta2-AR activity). The beta3-AR agonistic activity of SWR-0342SA was about 20 times stronger than its beta1-AR agonistic activity. Similarly, SWR-0342SA enhanced the accumulation of cAMP in Chinese hamster ovary (CHO) cells expressing human beta1- and beta3-ARs, while having no effect in CHO cells expressing beta2-ARs. Adenylyl cyclase stimulation by SWR-0342SA in CHO cells expressing beta3-ARs was about 35 times higher than that in CHO cells expressing beta1-ARs. With regards to anti-obesity and anti-diabetic activities, SWR-0342SA had no effect on body weight or food intake, but slightly decreased the fat pads weight in KK-Ay mice, an animal model of obesity and non-insulin-dependent diabetes mellitus (NIDDM). On the other hand, SWR-0342SA significantly decreased both blood glucose (to about 46% of control) and serum insulin levels (to about 40% of control) in KK-Ay mice. These results indicated that SWR-0342SA is a selective beta3-AR agonist, and possesses potent anti-diabetic activity, and that the anti-obesity activity is inferior to the anti-diabetic activity.

Acetates↗